Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine , Chinese Academy of Medical Sciences & Peking Union Medical College , Tianjin 300192 , P. R. China.
Department of Pharmacy , Affiliated Hospital of Logistics University of PAP , Tianjin 300162 , P. R. China.
ACS Appl Mater Interfaces. 2019 Jan 9;11(1):331-339. doi: 10.1021/acsami.8b18425. Epub 2018 Dec 28.
Supramolecular hydrogels of self-assembling peptide-drug conjugates have been considered as effective self-delivery drug systems for cancer therapy in recent years. Here, a novel self-assembling peptide-based supramolecular hydrogel was developed by simultaneously conjugating small-molecule drug chlorambucil (CRB) and peptide drug tyroservatide (YSV) to the self-assembling peptide. The resulting hydrogel with a nanofiber structure showed enhanced stability against proteinase K degradation and an improved cellular uptake performance in comparison with the free molecules. As a consequence, it exhibited enhanced antitumor efficiency both in vitro and in vivo with favorable biocompatibility. This biocompatible self-delivery drug system could not only significantly improve the delivery efficiency of the small-molecule drugs but also adequately synergize the antitumor effect of CRB and YSV, inspiring the design of new strategies of cancer combination therapy.
近年来，自组装肽-药物偶联物的超分子水凝胶已被认为是癌症治疗中有效的自递药系统。在这里，通过同时将小分子药物苯丁酸氮芥 (CRB) 和肽药物酪丝缬肽 (YSV) 连接到自组装肽上，开发了一种新型的基于自组装肽的超分子水凝胶。与游离分子相比，具有纳米纤维结构的所得水凝胶对蛋白酶 K 的降解具有增强的稳定性和改善的细胞摄取性能。因此，它在体外和体内均表现出增强的抗肿瘤效率，同时具有良好的生物相容性。这种具有生物相容性的自递药系统不仅可以显著提高小分子药物的递送效率，而且可以充分协同 CRB 和 YSV 的抗肿瘤作用，为癌症联合治疗的新策略设计提供了启示。
